There has been considerable recent interest in interactions between the nervous and immune systems, but the emphasis has largely been on nervous system effects on the immune system. Effective interaction between the two systems requires two-way communication. This proposal focusses on messengers from the immune system to central nervous system. Previous studies have suggested that there are electrophysiological and neurochemical changes in hypothalamic neurons during an immune response. We have shown that cerebral catecholaminergic neurons respond to administration of Newcastle disease virus (NDV) and to infection with influenza virus. Both these treatments also elevate plasma corticosterone. The monokine, interleukin-1 (IL-1), is known to be produced by macrophages following NDV administration, and during immune challenges. IL-1 is considered to be the endogenous pyrogen causing the fever response to infection. It has also been shown to activate the pituitary-adrenal axis. Thus IL-1 is a good candidate for a messenger from the immune system to the CNS. Consistent with this, pilot data indicate that IL-1 administration to mice can produce a selective activation of cerebral noradrenergic systems, especially in the hypothalamus. We proposed to characterize further the response of cerebral noradrenergic neurons to administration of viruses, of antigens and IL-1, to determine the anatomical specificity and temporal characteristics. We also plan to investigate whether IL-1 is the endogenous mediator of the viral-induced increase of plasma corticosterone and the activation of cerebral norepinephrine metabolism, using antibody to IL-1 and certain peptide fragments of IL-1 considered to be antagonists. The results of these studies will greatly enhance our understanding of immune system communication with the nervous system, and may identify the first immune messenger to the CNS.